(A) Under normal growth conditions, stimulatory signals from the insulin receptor activate the enzyme phosphoinositide kinase (PI3-kinase), which phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3), a lipid signaling molecule. Downstream, PIP3 activates several effectors, including the proto-oncogene product PKB/Akt. The role of PTEN is to dephosphorylate PIP3, acting as a negative control on PKB/Akt activation.

(B) If a mutation in PTEN renders it unable to carry out its phosphatase function, PIP3 can no longer be deactivated, so continues to propagate its signal downstream. This may result in the continued activation of PKB/Akt , which, in combination with other factors, could lead to increased cell growth and possible tumor development.